Stereotactic Body Radiation Therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience

Patients eligible for study inclusion had histologically-confirmed adenocarcinoma of the prostate treated per our institutional protocol. Exclusion criteria included clinical stage T3, involved lymph nodes or distant metastases on imaging and/or prior pelvic radiotherapy. Institutional IRB approval was obtained for retrospective review of data that was prospectively collected in our institutional database.

Four gold fiducials were placed into the prostate. Seven days after fiducial placement, patients underwent MR imaging followed shortly thereafter by a thin-cut CT scan. Fused CT and MR images were used for treatment planning. The clinical target volume (CTV) included the prostate and the proximal seminal vesicles (to the point where the seminal vesicles separate). The PTV equaled the CTV expanded 3 mm posteriorly and 5 mm in all other dimensions. The prescription dose was 35–36.25 Gy to the PTV delivered in five fractions of 7–7.25 Gy corresponds to a tumor EQD2 of approximately 85–90 Gy assuming an α/β ratio of 1.5. In general, older patients with poor baseline urinary function were treated with 35 Gy.

Treatment plans were composed of hundreds of pencil beams using one to two circular collimator to generate highly conformal plans (mean new conformity index of 1.28 [range, 1.12-1.59]). Plans were inhomogeneous by design (mean homogeneity index of 1.29 [range, 1.23-1.42]) to minimize dose to adjacent critical structures (Figure 1a). However, the prescription isodose line was limited to ≥ 75% to restrict the maximum prostatic urethra dose to 133% of the prescription dose. The rectum, bladder, testes, penile bulb and membranous urethra were contoured and evaluated with dose-volume histogram analysis during treatment planning using Multiplan (Accuray Inc., Sunnyvale, CA) inverse treatment planning. A typical dose-volume histogram is shown in Figure 1b and critical structure dose constraints are shown in Table 1. To minimize the risk of local recurrence, no attempt was made to limit the dose to the prostatic urethra or neurovascular bundles [9, 10]. Radiation was delivered every other day to a mean prescription isodose line of 77% (range, 75-81%) in 5 approximately 1 hour long treatments, with a mean treatment duration of 10.6 days (range, 5–16 days). On average, 247 beams were employed (range, 199–289 beams) to treat the mean prescription volume of 135 cc (range, 61–258 cc) with mean percent target coverage of 95.20% (range, 93.65-96.95%). Target position was verified every 30–60 seconds during treatment using paired, orthogonal kV images (total imaging effective dose equals 17.5 mSv).

Prostate-specific antigen (PSA) and total testosterone levels were obtained before treatment, one month after the completion of SBRT, and during routine follow-up visits every 3 months for the first year and every six months for the second year of follow-up. Alpha-antagonist, antidiarrheal and phosphodiesterase type 5 (PDE5) inhibitor utilization was documented at each visit.

Toxicity was prospectively documented at follow-up visits using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. Acute toxicity was defined as experiencing toxicity during or within 6 months of radiation therapy. Late toxicity was defined as occurring at least 6 months after delivery of radiation therapy. Transient and chronic late toxicities were included. The genitourinary toxicities analyzed were hematuria, dysuria, incontinence, urinary urgency/frequency and retention. The gastrointestinal toxicities analyzed were bowel frequency/urgency, proctitis and rectal bleeding. In general, Grade 1 toxicity represents minimal side effect not requiring medications for symptom control. Pre-treatment symptoms were counted as Grade 1 toxicity if they increased in severity. Grade 2 toxicity indicates symptoms requiring new medication (i.e. alpha-antagonist or antidiarrheal) or increase in dose of previously prescribed medication. Grade 3 indicates complications requiring minor surgical intervention (i.e., transurethral resection or laser coagulation). At each follow-up visit, toxicity events were scored independently for each of the different toxicity types and the highest GU and GI toxicity was determined for each patient.

Quality of life (QOL) was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. The Medical Outcomes Study Short Form-12 Health Survey (SF-12) [11], which contains two subscales, the Mental Component Summary (MCS) and the Physical Component Summary (PCS), with higher values indicating better quality of life. AUA scores range from 0–35 with higher values representing worsening urinary symptoms [12]. SHIM scores range from 0–25 with lower values representing worsening sexual symptoms [13].

Student’s t-test and chi-square analysis were used to assess differences in ongoing PSA, testosterone and quality of life scores (SF-12, AUA and SHIM) in comparison to baseline. Sample medians and ranges were used to describe continuous variables including PSA and testosterone. Based upon published results, a benign PSA bounce was defined as a PSA rise of 0.2 ng/mL or more above its previous nadir with a subsequent decline to that nadir or lower [14]. Actuarial likelihood estimates for late toxicities were determined using the Kaplan-Meier method. The highest GU or GI toxicity available for each patient was evaluated for the actuarial analysis. SF-12 analysis with norm-based scores (Mean = 50, standard deviation = 10) [15] was performed using IBM SPSS Statistics 20. The minimally important difference (MID) in AUA score was defined as a change of one-half standard deviation (SD) from the baseline [16]. As previously reported, late urinary symptom flare was defined as an increase of ≥ 5 points above baseline with a degree of severity in the moderate to severe range (AUA score ≥ 15) [17]. The flare was considered resolved when either the AUA score dropped to < 15 or the score returned to < 5 points above the patient’s pretreatment baseline. Erectile dysfunction (ED) was categorized into five categories of severity based on the patient’s SHIM score: no ED (22–25), mild ED (17–21), mild to moderate (12–16), moderate (8–11) and severe (1–7) [18]. Patients were considered potent if they scored ≥ 10 on the SHIM [18]. To limit the effect of attrition bias, statistical analysis was limited to time points in which ≥ 80% of the patient data were available.